5-chloro-2-(thiazol-4-yl)-1H-benzoimidazole | 142383-75-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 5-chloro-2-(thiazol-4-yl)-1H-benzoimidazole
• 英文别名: 5-Chlorothiabendazole；4-(6-chloro-1H-benzimidazol-2-yl)-1,3-thiazole
• CAS: 142383-75-3
• 化学式: C₁₀H₆ClN₃S
• 分子量: 235.697
• InChiKey: YTPUQGNBJYGJTB-UHFFFAOYSA-N

物化性质

• 熔点：
  238-240 °C(Solv: ethanol (64-17-5); water (7732-18-5))
• 沸点：
  475.1±43.0 °C(Predicted)
• 密度：
  1.520±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、乙醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-chloro-2-(thiazol-4-yl)-1H-benzoimidazole 、 2-氰基-4'-溴甲基联苯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.75h， 以27%的产率得到4'-(5-chloro-2-thiazol-4-yl-benzoimidazle-1-ylmethyl)biphenyl-2-carbonitrile
  参考文献：
  名称：

  NaOCl介导的通过分子内胺化反应制备噻菌灵的实用方法

  摘要：

  从易于获得的苯胺和4-氰基噻唑合成了一系列新型的氯化噻苯达唑（6a - m），产率中等至良好。使用1 H NMR，13 C NMR，IR和质谱对所有合成的化合物进行全面表征。另外，化合物（6f）的结构通过单晶X射线衍射确认。另外，使用我们优化的条件对2-取代的苯并咪唑和2-苯基苯并噻唑的合成进行了研究，结果在本文中给出。

  DOI：

  10.1016/j.tetlet.2017.07.086
• 作为产物：
  描述：

  3-氯苯胺 在 盐酸 、 sodium carbonate 作用下， 以 甲醇 、 水 、 邻二氯苯 为溶剂， 反应 5.33h， 生成 5-chloro-2-(thiazol-4-yl)-1H-benzoimidazole
  参考文献：
  名称：

  NaOCl介导的通过分子内胺化反应制备噻菌灵的实用方法

  摘要：

  从易于获得的苯胺和4-氰基噻唑合成了一系列新型的氯化噻苯达唑（6a - m），产率中等至良好。使用1 H NMR，13 C NMR，IR和质谱对所有合成的化合物进行全面表征。另外，化合物（6f）的结构通过单晶X射线衍射确认。另外，使用我们优化的条件对2-取代的苯并咪唑和2-苯基苯并噻唑的合成进行了研究，结果在本文中给出。

  DOI：

  10.1016/j.tetlet.2017.07.086

文献信息

• Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives and Analogs Targeting the NLRP3 Inflammasome
  作者：Liangkun Pan、Nan Hang、Chao Zhang、Yu Chen、Shuchun Li、Yang Sun、Zhongjun Li、Xiangbao Meng

  DOI：10.3390/molecules22020213

  日期：——

  synthesized and their antiinflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family，pyrin domain-containing 3，also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by antiproduction of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized

  合成了一系列噻唑的苯并[d]咪唑类似物，并评估了它们对炎性体NLRP3（核苷酸结合结构域富含亮氨酸的重复序列，含有蛋白质家族，含有pyrin结构域的家族3，也称为冻菌素或NALP3）的抗炎活性。 。通过产生IL-1β鉴定了两种先导化合物TBZ-09和TBZ-21。在第二轮生物学评估中，以铅为基础，又合成了34种化合物，并研究了它们的体外抗炎活性。几种化合物被鉴定为可以以剂量依赖的方式降低IL-1β表达的抗炎药。初步的构效关系也总结在这里。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF THIABENDAZOLE<br/>[FR] PROCÉDÉ PERFECTIONNÉ POUR LA PRÉPARATION DE THIABENDAZOLE
  申请人：HIKAL LTD

  公开号：WO2019016834A1

  公开（公告）日：2019-01-24

  The present invention relates to an improved process for preparing thiabendazole of formula (I) with high yield, high purity, in economical and commercially viable manner for agricultural and pharmaceutical use.

  本发明涉及一种改进的工艺，用于以高产率、高纯度、经济和商业可行的方式制备公式（I）的硫苯咪唑，以供农业和制药用途。
• Metal-Mediated Inhibition of <i>Escherichia </i><i>c</i><i>oli</i> Methionine Aminopeptidase:  Structure−Activity Relationships and Development of a Novel Scoring Function for Metal−Ligand Interactions
  作者：Rolf Schiffmann、Alexander Neugebauer、Christian D. Klein

  DOI：10.1021/jm050476z

  日期：2006.1.1

  We report the discovery of thiabendazole as a potent inhibitor (K-i = 0.4 mu M) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis and pharmacological evaluation of thiabendazole congeners with activity in the upper nanomolar range. Elucidation of the X-ray structure of ecMetAP in complex with thiabendazole and an unrelated inhibitor that was independently described by another group showed that that both compounds bind to an additional Coll ion at the entrance of the active site. This unexpected finding explains the inactivity of the compounds under in vivo conditions. It also allows us to discuss the structure-activity relationships of this series of compounds in a meaningful way, based upon docking runs with an auxiliary metal ion. We describe a new scoring function for the evaluation of metal-mediated inhibitor binding that, unlike the previously used scoring function implemented in the docking program, allows us to distinguish between active and inactive compounds. Finally, conclusions for the structure-based design of in vivo-active inhibitors of ecMetAP are drawn.
• Synthesis and biological evaluation of thiabendazole derivatives as anti-angiogenesis and vascular disrupting agents
  作者：Chao Zhang、Bo Zhong、Simin Yang、Liangkun Pan、Siwang Yu、Zhongjun Li、Shuchun Li、Bin Su、Xiangbao Meng

  DOI：10.1016/j.bmc.2015.03.085

  日期：2015.7

  Thiabendazole, already approved by FDA for oral use as an anti-fungal and anti-helminthic drug since 1967, has recently been repurposed as a vascular disrupting agent. By optimization of the structure of the lead compound, we successfully identified compound TBZ-19 and the new derivative is over 100-fold more potent than the lead compound against the growth of four different cell lines ( A549, HCT-116, HepG2 and HUVECs). The most potent two candidates TBZ-07 and TBZ-19, exhibiting moderate inhibitory cell proliferation activity, were also verified as anti-angiogenesis and vascular disrupting agents. Therefore, TBZ-07 and TBZ-19 would be promising candidates with vasculature targeting activity and merit further development. (C) 2015 Elsevier Ltd. All rights reserved.